Spontaneous, collective activation of neurons is emerging as a ubiquitous, salient property of immature neural networks throughout the brain. Because of the profound and long-lasting effects that early activation patterns can have on the structure and function of the brain later in life, knowledge of normal and abnormal patterns is essential to deciphering the factors contributing to development of normal and abnormal circuit properties. A specific form of collective neuronal activation occurs in immature cerebral cortex in response to specific neuromodulators, as recently demonstrated in the investigator's laboratory. During these brief events, neuronal electrical activity spreads as a regenerative wave through cortical networks. They propose to directly address fundamental questions concerning the physiology and anatomy of waves in cortex by using state-of-the-art fluorescence imaging and patch clamp techniques on cortical slices. During these investigations they plan to: 1) identify the cortical brain regions and cell types responsible for generating cortical waves, 2) examine the signaling pathways involved in initiating this phenomenon, and 3) study the mechanisms that coordinate and spread activation among the cortical neurons participating in these events. They pursue these objectives believing that knowledge of the functional and anatomical basis of spontaneous neural activation in developing cortex may illuminate the underlying causes of specific dysfunctions associated with this part of the brain.